4-168497116-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001166108.2(PALLD):​c.-161A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 151,926 control chromosomes in the GnomAD database, including 9,239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 9238 hom., cov: 31)
Exomes 𝑓: 0.28 ( 1 hom. )

Consequence

PALLD
NM_001166108.2 5_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.349
Variant links:
Genes affected
PALLD (HGNC:17068): (palladin, cytoskeletal associated protein) This gene encodes a cytoskeletal protein that is required for organizing the actin cytoskeleton. The protein is a component of actin-containing microfilaments, and it is involved in the control of cell shape, adhesion, and contraction. Polymorphisms in this gene are associated with a susceptibility to pancreatic cancer type 1, and also with a risk for myocardial infarction. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]
DDX60L (HGNC:26429): (DExD/H-box 60 like) This gene encodes a member of the DExD/H-box helicase family of proteins, a subset of the super family 2 helicases. Members of the DExD/H-box helicase family share a conserved functional core comprised of two RecA-like globular domains. These domains contain conserved motifs that mediate ATP binding, ATP hydrolysis, nucleic acid binding, and RNA unwinding. In addition to functions in RNA metabolism, members of this family are involved in anti-viral immunity and act as cytosolic sensors of viral nucleic acids. The protein encoded by this gene has been shown to inhibit hepatitis C virus replication in response to interferon stimulation in cell culture. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 4-168497116-A-T is Benign according to our data. Variant chr4-168497116-A-T is described in ClinVar as [Benign]. Clinvar id is 348020.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PALLDNM_001166108.2 linkuse as main transcriptc.-161A>T 5_prime_UTR_variant 1/22 ENST00000505667.6
LOC107986198XR_001741448.3 linkuse as main transcriptn.281-4231T>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PALLDENST00000505667.6 linkuse as main transcriptc.-161A>T 5_prime_UTR_variant 1/221 NM_001166108.2 A2Q8WX93-9

Frequencies

GnomAD3 genomes
AF:
0.338
AC:
51366
AN:
151772
Hom.:
9213
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.366
Gnomad AMI
AF:
0.394
Gnomad AMR
AF:
0.479
Gnomad ASJ
AF:
0.301
Gnomad EAS
AF:
0.603
Gnomad SAS
AF:
0.290
Gnomad FIN
AF:
0.276
Gnomad MID
AF:
0.354
Gnomad NFE
AF:
0.284
Gnomad OTH
AF:
0.344
GnomAD4 exome
AF:
0.278
AC:
10
AN:
36
Hom.:
1
Cov.:
0
AF XY:
0.182
AC XY:
4
AN XY:
22
show subpopulations
Gnomad4 EAS exome
AF:
1.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.500
Gnomad4 NFE exome
AF:
0.233
GnomAD4 genome
AF:
0.339
AC:
51437
AN:
151890
Hom.:
9238
Cov.:
31
AF XY:
0.343
AC XY:
25458
AN XY:
74246
show subpopulations
Gnomad4 AFR
AF:
0.366
Gnomad4 AMR
AF:
0.479
Gnomad4 ASJ
AF:
0.301
Gnomad4 EAS
AF:
0.603
Gnomad4 SAS
AF:
0.290
Gnomad4 FIN
AF:
0.276
Gnomad4 NFE
AF:
0.284
Gnomad4 OTH
AF:
0.348
Alfa
AF:
0.316
Hom.:
994
Bravo
AF:
0.360
Asia WGS
AF:
0.458
AC:
1590
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2015- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Pancreatic cancer, susceptibility to, 1 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
0.55
DANN
Benign
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2710836; hg19: chr4-169418267; API